In this review, an overview is provided on the current achievements regarding the interplay between rumen digestive disorders and diet-induced inflammation in dairy cattle. It starts with a review of factors favoring the disturbances in the rumen metabolism, which culminate with development of sub-acute rumen acidosis (SARA). The latter digestive disorder is often linked to greater metabolic stress of gastrointestinal (GI) microbiota and lowered fiber digestion, as well as with disruption of the barrier functions of the GI epithelia, which open the route of deleterious molecules to translocate from the GI lumen into the portal system. A model is suggested to illustrate the mechanisms of the involvement of digestive disorders in the disruption of the host"s inner homeostasis leading to activation of acute phase response (APR). The latter is part of multifaceted innate immune and metabolic responses of the host. According to this model, endotoxin, its toxicity, and other metabolic compounds of microbial origin are regarded as important immunogenic components of GI tract, which when favored by disruption of host barriers triggers a systemic APR. Although the activation of an APR is viewed as a protective reaction aiming to reestablish the disturbed homeostasis, the presence of inflammatory state over long periods might be associated with negative consequences for the host. The review concludes that prolonged systemic inflammation can: (1) cause significant changes in the energy and lipid metabolism in different body tissues, (2) lead to the development of refractory states associated with immune suppression and increased susceptibility to various diseases, and (3) artificially increase host"s requirements in energy and nutrients, lowering the efficiency of energy and feed use by the animal. The paper emphasizes the critical role that formulation of healthy diets plays for curbing down inflammation and enhancing metabolic health of dairy cows.